Gabapentin (“GBP”), 1-(aminomethyl)cyclohexaneacetic acid is described according to the following formula:
GBP is a white to off-white crystalline solid with a pKal of 3.7 and a pKa2 of 10.7. GBP is marketed by Pfizer under the trade name Neurontin®.
GBP is used in the treatment of cerebral diseases such as epilepsy. In animal models of analgesia, GBP prevents allodynia (pain-related behavior in response to a normally innocuous stimulus) and hyperalgesia (exaggerated response to painful stimuli). GBP also decreases pain related responses after peripheral inflammation. Animal test systems designed to detect anticonvulsant activity, proved that GBP prevents seizures as do other marketed anticonvulsants.
Gabapentin enacarbil (“GBPE”), 1-{[(α-isobutanoyloxyethoxy)carbonyl]-aminomethyl}-1-cyclohexane acetic acid, is a transported prodrug of GBP and is described according to the following formula:

GBPE was developed to improve some of the bioavailability limitations that are known in GBP. GBPE is recognized by high-capacity transport proteins expressed all along the intestinal tract, making it suitable for sustained-release formulation for colonic absorption. After its absorption in the blood, GBPE is rapidly converted to GBP.
A coupling process of 1-haloalkyl carbamates or carbonates with carboxylic acid is used in synthetic chemistry and particularly in medicinal chemistry, as exemplified in J. Med. Chem. 1999, 42, pages 3994-4000 and J. Med. Chem. 1988, 31, pages 318-322, as a way to construct the diacid-acetal skeleton. The process is described in scheme 1 below:

The use of a coupling agent in the process depicted above is known in the art with the use of coupling agents such as mercury acetate, mercury oxide and silver oxide. This is exemplified in U.S. Pat. No. 6,818,787 (“the '787 patent”). The '787 patent describes a process for preparing GBPE according to scheme 1 using silver oxide (Ag2O) as a coupling agent. The process for preparing compound 18 from compound 16 described in the '787 patent and illustrated in scheme 2 below is a two step process, where compound 17 is prepared separately.

GBPE and processes for its preparation are described in U.S. Pat. Nos. 6,818,787, 7,232,924 and 7,227,028, which are incorporated herein by reference.
Like any synthetic compound, gabapentin enacarbil can contain extraneous compounds or impurities. These impurities may include unreacted starting materials, by-products of the reaction, products of side reactions, and/or degradation products.
Impurities in gabapentin enacarbil or any active pharmaceutical ingredient (“API”) are undesirable and, in extreme cases, might be harmful to a patient being treated with a dosage form of the API.
There is a need in the art for an improved process for preparing GBPE and its intermediates, and processes for purifying GBPE.